Effect of a Low-Dose Contraceptive Patch on Efficacy, Bleeding Pattern, and Safety: A 1-Year, Multicenter, Open-Label, Uncontrolled Study
Tóm tắt
This Phase III, uncontrolled, open-label, multicenter study was conducted to investigate the contraceptive efficacy, bleeding pattern, and cycle control of a novel once-a-week contraceptive patch, delivering low-dose ethinyl estradiol (EE) and gestodene (GSD) at the same systemic exposure seen after oral administration of a combined oral contraceptive containing 0.02 mg EE/0.06 mg GSD. Participants were women aged 18 to 35 years, all of whom received the EE/GSD patch for 13 cycles each of 21 treatment days (one patch per week for 3 weeks) followed by a 7-day, patch-free interval. The primary efficacy variable was the occurrence of unintended pregnancies during the study period as assessed by life table analysis and the Pearl Index. Secondary efficacy variables were days with bleeding during four 90-day reference periods and during 1 treatment year, bleeding pattern, and cycle control. The Kaplan-Meier probability of contraceptive protection after 364 treatment days was 98.8% and the adjusted Pearl Index was 0.81. The percentage of participants with intracyclic bleeding/spotting decreased over time, from 11.4% to 6.8% in cycles 1 and 12, respectively. Almost all participants (range: 90.8%-97.6%) experienced withdrawal bleeding across the study period. Compliance was very high (mean: 97.9%; median: 100%). The most frequent adverse events were headache (9.5%) and application site reaction (8.5%); no clinically significant safety concerns were observed. Results suggest the EE/GSD patch is highly effective in preventing pregnancy. Menstrual bleeding pattern was favorable and within the ranges expected of a healthy female population. The patch was well tolerated and treatment compliance was high.
Tài liệu tham khảo
Nelson HD. Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review. JAMA. 2004; 291(13):1610–1620.
Janssen-Cilag. Evra® transdermal patch. Summary of Product Characteristics; 2012. http://www.medicines.org.uk/emc/medicine/12124/spc. Accessed April 17, 2014.
Bayer. Apleek®. Summary of Product Characteristics. http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1394776320327.pdf. Accessed April 17, 2014.
UN Department of Economic and Social Affairs Population Division. World contraceptive use. http://www.un.org/esa/population/publications/contraceptive2011/contraceptive2011.htm. Accessed April 17, 2014.
Aubeny E, Buhler M, Colau JC, Vicaut E, Zadikian M, Childs M. The Coraliance study: non-compliant behavior. Results after a 6-month follow-up of patients on oral contraceptives. Eur J Contracept Reprod Health Care. 2004;9(4):267–277.
Goldzieher JW, Brody SA. Pharmacokinetics of ethinyl estradiol and mestranol. Am J Obstet Gynecol. 1990;163(6 pt 2): 2114–2119.
Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. 2005;(8 suppl 1): 3–63.
Jung-Hoffmann C, Kuhl H. Intra- and interindividual variations in contraceptive steroid levels during 12 treatment cycles: no relation to irregular bleedings. Contraception. 1990;42(4):423–438.
Burkman RT. Transdermal hormonal contraception: benefits and risks. Am J Obstet Gynecol. 2007;197(2):134 e131–e136.
Heger-Mahn D, Warlimont C, Faustmann T, Gerlinger C, Klipping C. Combined ethinylestradiol/gestodene contraceptive patch: two-center, open-label study of ovulation inhibition, acceptability and safety over two cycles in female volunteers. Eur J Contracept Reprod Health Care. 2004;9(3):173–181.
Coelingh Bennink HJ. Are all estrogens the same? Maturitas. 2004;47(4):269–275.
Barbosa IC, Filho CI, Faggion D Jr, Baracat EC. Prospective, open-label, noncomparative study to assess cycle control, safety and acceptability of a new oral contraceptive containing gestodene 60 microg and ethinylestradiol 15 microg (Minesse). Contraception. 2006;73(1):30–33.
Kaplan B. Desogestrel, norgestimate, and gestodene: the newer progestins. Ann Pharmacother. 1995;29(7–8):736–742.
Wilde MI, Balfour JA. Gestodene. A review of its pharmacology, efficacy and tolerability in combined contraceptive preparations. Drugs. 1995;50(2):364–395.
Benagiano G, Primiero FM, Farris M. Clinical profile of contraceptive progestins. Eur J Contracept Reprod Health Care. 2004;9(3):182–193.
Beligotti F, Gordon K. Findings from the International ‘I plan on . . . survey’: women’s awareness, misconceptions, and preferences regarding their contraceptive options. Eur J Contracept Reprod Health Care. 2012;17(S1):S98.
Glasier A, Scorer J, Bigrigg A. Attitudes of women in Scotland to contraception: a qualitative study to explore the acceptability of long-acting methods. J Fam Plann Reprod Health Care. 2008; 34(4):213–217.
Schrager S. Abnormal uterine bleeding associated with hormonal contraception. Am Fam Physician. 2002;65(10):2073–2080.
Jakimiuk AJ, Crosignani PG, Chernev T, et al. High levels of women’s satisfaction and compliance with transdermal contraception: results from a European multinational, 6-month study. Gynecol Endocrinol. 2011;27(10):849–856.
Weisberg E. Developments in contraception. Expert Opin Pharmacother. 2014;15(2):203–210.
Reid R, Leyland N, Wolfman W, et al. SOGC clinical practice guidelines: oral contraceptives and the risk of venous thromboembolism: an update. J Obstet Gynaecol Can. 2010;32(12):1192–1204.
Vandenbroucke JP, Koster T, Briet E, Reitsma PH, Bertina RM, Rosendaal FR. Increased risk of venous thrombosis in oral contraceptive users who are carriers of factor V Leiden mutation. Lancet. 1994;344(8935):1453–1457.
Bitzer J, Amy JJ, Beerthuizen R, et al. Statement on combined hormonal contraceptives containing third- or fourth-generation progestogens or cyproterone acetate, and the associated risk of thromboembolism. J Fam Plann Reprod Health Care. 2013; 39(3):156–159.
Cole JA, Norman H, Doherty M, Walker AM. Venous thromboembolism, myocardial infarction, and stroke among transdermal contraceptive system users. Obstet Gynecol. 2007;109(2 pt 1):339–346.
Jick SS, Kaye JA, Russmann S, Jick H. Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol. Contraception. 2006; 73(3):223–228.
Lidegaard O, Nielsen LH, Skovlund CW, Lokkegaard E. Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10. BMJ. 2012;344:e2990.